The broad, long-term aims of this proposal are to develop applications of arene-metal pi complexes to the total synthesis of challenging molecular arrays that are components of important natural product molecules, and to develop new methodology for asymmetric synthesis based on chiral auxiliary-directed nucleophile additions to arene-metal complexes. The specific aims are listed as follows: (a) Continue investigations directed toward the applications of arene- Mn(CO)3 and arene-RuCp cations in the total synthesis of ristocetin A, a complex glycopeptide that is related to vancomycin and teicoplanin, the molecular structures of which present a challenging opportunity for the development of new and unique methodology for the construction of diary ethers having sensitive attached amino acid and peptide functionality. The glycopeptide targets are of considerable significance and are used as antibiotic active against gram positive bacteria. (b) Explore the applications of arene-metal complexes in the synthesis of enantiomerically pure 4,5-disubstituted cyclohexenones and related compounds, by means of chiral auxiliary-directed asymmetric nucleophile additions to the arene ligand. (c) Initiate studies on ruthenium-promoted intramolecular diary ether formation, and ruthenium-catalyzed diary ether formation, based on observations on the stoichiometric reactions of chloroarene-RuCp cations, which allow direct coupling of protected chloroarylamino acids with protected hydroxyarylamino acids and derived peptides. These methods allow the facile construction of useful building blocks for the synthesis of biologically active compounds such as K-13, which is an inhibitor of angiotensin converting enzyme (ACE). (d) Further develop the chemistry arene-FeCp cations (Cp=eta5- cyclopentadienyl) to allow selective functionalization of the aromatic ligand. The most challenging aspect of this chemistry is the development of methods for the conversion of cyclohexadienyl-FeCp complexes, that are formed by nucleophile addition to the arene ligand, to cyclohexenones and related molecules; studies to address this unsolved problem will be undertaken.